Andexanet alfa: Additional Phase II data

Data from 18 healthy volunteers in the third and fourth cohorts of a double-blind, placebo-controlled Phase II trial showed that a single IV bolus of andexanet alfa reversed the anticoagulant activity of once-daily 20 mg oral Xarelto rivaroxaban given for 6 days immediately following completion of treatment by 70% at the 600 mg dose of andexanet alfa and by 81% at the 720 mg dose of andexanet alfa. Patients in the 720 mg dose cohort also received a 4 mg/minute infusion of andexanet alfa for 1 hour following the single IV bolus. Additionally, andexanet alfa dose-dependently and rapidly reversed Xarelto-induced inhibition of thrombin generation and prolongation of both prothrombin time and activated clotting time. Andexanet alfa was well tolerated with no serious adverse events reported. Data were presented at the American Society of Hematology meeting in New Orleans. The company previously reported data from the first 2 cohorts evaluating 210 and 420 mg doses of andexanet alfa (see BioCentury, Nov. 18, 2013). This half, Portola plans to start Phase III testing with andexanet alfa.

In November, FDA granted breakthrough therapy designation for andexanet alfa to reverse the anticoagulant activity of Factor Xa inhibitors (see BioCentury, Dec. 9, 2013). Portola has a number of deals to evaluate the ability of andexanet alfa to reverse the anticoagulation activity of marketed Factor Xa inhibitors, including Xarelto from Bayer AG (Xetra:BAYN, Leverkusen, Germany) and partner Johnson & Johnson (NYSE:JNJ, New Brunswick, N.J.); Eliquis apixaban from Bristol-Myers Squibb Co. (NYSE:BMY, New York, N.Y.) and partner Pfizer Inc. (NYSE:PFE, New York, N.Y.); and edoxaban from Daiichi Sankyo Co. Ltd. (Tokyo:4568, Tokyo, Japan) (see BioCentury, Nov. 12, 2012; Feb. 11, 2013; & July 15, 2013). ...